Complementary suppression of T cell activation by peritoneal macrophages and CTLA-4-Ig.

Peritoneal macrophages suppressed T lymphocyte activation by amino acid catabolism. CTLA-4-Ig complemented this form of suppression by blocking the costimulation of T cells. Inhibition of the amino acid catabolizing enzymes or blockade of the IFNgamma signaling essential for macrophage-mediated suppression did not impact CTLA-4-Ig efficacy. Except for phytohemagglutinin, T cell responses to superantigen, mitogen, and anti-CD3 were further reduced when CTLA-4-Ig was combined with peritoneal macrophages. The combination of these complimentary forms of immune regulation potently suppresses adaptive immunity.